Pancreatic endocrine cells have been expected to be used as, for example, a material for regenerative therapies for diabetes or a material used for screening of diabetes drugs. In terms of the regenerative therapies, for example, it has been expected that β cells, which are one of the pancreatic endocrine cells and produce insulin, are administered to type I diabetes patients who are insulin-deficient.
Therefore, keen demand has arisen for developing a method for preparing pancreatic endocrine cells in vitro in large quantities.
There has been proposed a method for producing β cells using embryonic stem cells (hereinafter may be referred to as “ES cells”) or induced pluripotent stem cells (hereinafter may be referred to as “iPS cells”). However, the method has the following problems. Firstly, the method is complicated because culturing environments are needed to be properly adjusted by, for example, adding various inhibitors involved in development or differentiation to a cell culture medium. Secondly, the method may be unreproducible. Thirdly, the method is problematic in terms of efficiency because other cells than the β cells are also produced. Finally, the method takes at least 21 days to 30 days to produce the β cells, that is, the β cells are not capable of being produced in a short period of time.
Therefore, at present, keen demand has arisen for promptly providing a method for producing pancreatic endocrine cells, the method being simple, easily reproduced, excellent in production efficiency, and capable of producing the pancreatic endocrine cells in a short period of time.
Note that, GLIS1 (GLIS family zinc finger 1), which is a member of the GLIS family, has been known to improve an establishment improving efficiency of iPS cells (see, e.g., PTL 1). GLIS3 (GLIS family zinc finger 3) has been known to be capable of being used for inducing differentiation of human pluripotent or multipotent cells into functional pancreatic β cells that produce insulin (see, e.g., PTL 2). Ngn3 (Neurogenin3) has been known to be transiently expressed in pancreatic endocrine cells during pancreas development.
However, it has not been that the GLIS family or the Ngn3 transform somatic cells into pancreatic endocrine cells directly without undergoing the stem cell stage.